CHEK2 Mutations and Breast Cancer

• Truncating CHEK2 mutations (such as the c.1100delC mutation):
  • Are considered rare:
    • Moderate penetrance mutations
• The lifetime risk of developing breast cancer with these mutations:
  • Is three times higher than the general population:
    • This means that the majority of patients with these mutations will not develop breast cancer:
      • Many of the cancers that do develop may be:
        • Sporadic and not related to the mutation
• Patients with these mutations should be counseled about their risk and the available risk management strategies:
  • Those with a significant family history of breast cancer should be counseled regarding high risk breast cancer screening:
    • Annual mammogram with consideration of annual MRI starting at age 40 or modified to an earlier age based on family history) 
  • Counseled regarding high risk breast cancer prevention strategies, including:
    • Chemoprevention and prophylactic surgery:
      • It should be emphasized that there is less absolute risk-reduction benefit with:
        • Prophylactic surgery compared to high-penetrance mutations like BRCA mutations
      • Recommendations should be based on:
        • Patient’s family history
    • National Comprehensive Cancer Network guidelines should be followed with recommendation for high-risk screening, including:
      • Colon cancer screening recommendations:
        • Among individuals with a CHEK2 mutation
• References:
• Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet. 2008;40(1):17-22.
• Desmond A, Kurian AW, Gabree M, Mills MA, Anderson MJ, Kobayashi Y, et al. Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1(7):943-951.
• Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg. 2018;153(12):1145-1146.
• Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-588.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncology #BreastCancer #HereditaryBreastCancer #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital